Background— Granulocyte-macrophage colony-stimulating factor (GM-CSF) was recently shown to increase collateral flow index in patients with coronary artery disease. Experimental models showed beneficial effects of GM-CSF on collateral artery growth in the peripheral circulation. Thus, in the present study, we evaluated the effects of GM-CSF in patients with peripheral artery disease. Methods and Results— A double-blinded, randomized, placebo-controlled study was performed in 40 patients with moderate or severe intermittent claudication. Patients were treated with placebo or subcutaneously applied GM-CSF (10 μg/kg) for a period of 14 days (total of 7 injections). GM-CSF treatment led to a strong increase in total white blood cell count and C-reactive protein. Monocyte fraction initially increased but thereafter decreased significantly as compared with baseline. Both the placebo group and the treatment group showed a significant increase in walking distance at day 14 (placebo: 127±67 versus 184±87 meters, P =0.03, GM-CSF: 126±66 versus 189±141 meters, P =0.04) and at day 90. Change in walking time, the primary end point of the study, was not different between groups. No change in ankle-brachial index was found on GM-CSF treatment at day 14 or at day 90. Laser Doppler flowmetry measurements showed a significant decrease in microcirculatory flow reserve in the control group ( P =0.03) and no change in the GM-CSF group. Conclusions— The present study does not support the use of GM-CSF for treatment of patients with moderate or severe intermittent claudication. Issues that need to be addressed are dosing, the selection of patients, and potential differences between GM-CSF effects in the coronary and the peripheral circulation.

Peripheral arterial disease (PAD) is an important manifestation of systemic atherosclerosis, with diabetes being one of its most significant risk factors. Owing to medial arterial calcification (MAC), the ankle–brachial index (ABI) is not always a reliable tool for detecting PAD. Arterial Doppler flow parameters, such as systolic maximal acceleration (ACCmax) and relative pulse slope index (RPSI), may serve as effective surrogates to detect stenosis-induced flow alteration. In the present study, ACCmax and RPSI were prospectively evaluated in 166 patients (304 arteries) with clinical suspicion of PAD, including 76 patients with and 90 patients without diabetes. In the overall sample, the sensitivity of ACCmax (69%) was superior to that of ABI (58%) and RPSI (56%). In patients with diabetes, the sensitivity of ACCmax (57%), ABI (56%) and RPSI (57%) were similar, though a parallel test taking both ACCmax and RPSI into account further increased sensitivity to 68%. The specificity (98%) and accuracy (78%) of ACCmax were superior to those of ABI (83% and 70%, respectively), as were the specificity (95%) and accuracy (77%) of RPSI in patients with diabetes. The diagnostic properties of ACCmax and RPSI were superior to those of ABI for detecting PAD in patients with diabetes. Our acceleration algorithm (Gefäßtachometer®) provides a rapid, safe, noninvasive tool for identifying PAD in patients with diabetes.

In this study, we provide direct functional evidence for the stimulation of coronary arteriogenesis via ECP in patients with stable coronary artery disease. These data might open a novel noninvasive and preventive treatment avenue for patients with non-acute vascular stenotic disease.